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. 2021 Feb;17(5):491-501.
doi: 10.2217/fon-2020-0737. Epub 2020 Nov 10.

First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811

Hyun Cheol Chung  1 , Yung-Jue Bang  2 , Charles S Fuchs  3 , Shu-Kui Qin  4 , Taroh Satoh  5 , Kohei Shitara  6 , Josep Tabernero  7 , Eric Van Cutsem  8 , Maria Alsina  7 , Zhu Alexander Cao  9 , Jia Lu  9 , Pooja Bhagia  9 , Chie-Schin Shih  9 , Yelena Y Janjigian  10
Affiliations

First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811

Hyun Cheol Chung et al. Future Oncol. 2021 Feb.

Abstract

Treatment options for patients with HER2-positive advanced gastric cancer are limited, and the prognosis for these patients is poor. Pembrolizumab has demonstrated promising antitumor activity in patients with advanced gastric or gastroesophageal junction adenocarcinoma as monotherapy, in combination with chemotherapy and in combination with trastuzumab. Combining pembrolizumab with trastuzumab and chemotherapy may therefore provide a benefit for patients with advanced HER2-positive gastric cancer. Here we aimed to describe the design of and rationale for the randomized, double-blind, placebo-controlled Phase III KEYNOTE-811 study, which will evaluate the efficacy and safety of pembrolizumab or placebo in combination with trastuzumab and chemotherapy as first-line treatment for patients with advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma. Clinical trial registration: NCT03615326 (ClinicalTrials.gov).

Keywords: chemotherapy; first-line therapy; gastric cancer; gastroesophageal junction cancer; human epidermal growth factor receptor 2; pembrolizumab; trastuzumab.

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Conflict of interest statement

Financial & competing interests disclosure

Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., NJ, USA. HC Chung reports grants to his institution and writing support from MSD during the conduct of the study. He also reports grants to his institution from Amgen, BeiGene, BMS/Ono, GSK, Lilly, Merck-Serono, MSD and Taiho; honoraria from Lilly and Merck Serono; and consultation fees from Amgen, BeiGene, BMS, Celltrion, Gloria, Lilly, Merck Serono, MS, Quintiles, Taiho and Zymework outside the submitted work. Y-J Bang served in a consulting/advisory role for Astellas, AstraZeneca, Bayer, BeiGene, BMS, Daiichi Sankyo, Eli Lilly, Genentech/Roche, Genexine, GreenCross, Hanmi, Merck Serono, MSD, Novartis, Samyang Biopharm and Taiho, and grants (to the institution for clinical trials) from Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Boston Biomedical, BMS, CKD Pharma, Curis, Daiichi Sankyo, Eli Lilly, Five Prime, Genentech/Roche, Genexine Green Cross, GSK, MacroGenics, Merck Serono, MSD, Novartis, Ono, Pfizer, Taiho and Takeda outside the submitted work. CS Fuchs served in an advisory/consultancy role for Agios, Amylin Pharmaceuticals, Bain Capital, CytomX Therapeutics, Daiichi Sankyo, Eli Lilly, Entrinsic Health, EvolveImmune Therapeutics, Genentech, Merck, Taiho and Unum Therapeutics. He also serves as a director for CytomX Therapeutics and owns unexercised stock options for CytomX and Entrinsic Health. He is a co-founder of EvolveImmune Therapeutics and has equity in this private company. S-K Qin reports no conflict of interest. T Satoh reports grants from Astellas, BMS, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Gilead Sciences, MSD, Ono, Parexel, Taiho and Yakult Honsha; personal fees from Astellas, BMS, Chugai Pharmaceutical, Eli Lilly, MSD, Ono, Taiho, Takara Bio, Sanofi-Aventis and Yakult Honsha; and endorsed department from Chugai Pharmaceutical, Ono and Yakult Honsha. K Shitara served in an advisory role for AbbVie, Astellas, BMS, Eli Lilly, GSK, Merck Pharmaceutical, Novartis, Ono, Pfizer, Taiho and Takeda; received research funding from Astellas, Chugai Pharma, Dainippon Sumitomo Pharma, Daiichi Sankyo, Eli Lilly, Merck Pharmaceutical, Medi Science and Taiho and honoraria (lecture fees) from AbbVie, Novartis and Yakult. J Tabernero served in a scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, F. Hoffmann-La Roche Ltd, Sanofi, Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. E van Cutsem served in an advisory/consultancy role for Array, AstraZeneca, Bayer, Biocartis, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Halozyme, GSK, Pierre Fabre, Incyte, Ipsen, Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., NJ, USA., Merck KGaA, Novartis, Pierre Fabre, Roche, Servier, Sirtex and Taiho and reports grants (to his institution) from Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., NJ, USA., Merck KGaA, Novartis, Roche, and Servier. M Alsina reports honoraria from BMS, Lilly, MSD and Servier and served in an advisory/consultancy role for BMS, Lilly, MSD and Servier. ZA Cao reports employment at Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., NJ, USA. J Lu reports employment at Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., NJ, USA. Bhagia reports employment at Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., NJ, USA. CS Shih reports employment at and is a stockholder of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., NJ, USA. YY Janjigian reports advisory fees from Bristol Myers Squibb, Lilly, Merck, Merck Serono and Pfizer; and research expenses from Amgen, Bayer, Boehringer Ingelheim, Genentech, Lilly and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing and editorial assistance were provided by Holly C. Cappelli, PhD, CMPP, and Brian Szente, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co, NJ, USA.

Figures

Figure 1.
Figure 1.. KEYNOTE-811 study design.
(A) Global cohort. (B) Japan-specific S-1 + oxaliplatin cohort. CAPOX: Capecitabine + oxaliplatin; FP: 5-Fluorouracil + cisplatin; R: Randomization; SOX: S-1 + oxaliplatin.
See this image and copyright information in PMC

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